Compensatory Mechanisms Research Articles

Proxy involvement of Czech parents in education: inner tensions and situational burdens behind decisions to buy private tutoring

ABSTRACT While previous research on private tutoring has focused predominantly on its meso- or macro-level determinants, this qualitative study, anchored in the literature on parental involvement, explores proximal factors, including psychological and situational influences, that affect parental decisions to seek private tutoring. The study is based on semi-structured interviews with 65 Czech parents, who considered buying or had bought private tutoring for their child. It demonstrates that due to their internalised active parental role, parents feel a strong obligation to intervene when their educational expectations for their children are unmet. Private tutoring is considered when parents cannot or do not want be directly involved because of various barriers. Parents then use private tutoring as a compensatory mechanism, effectively outsourcing their involvement to a proxy: a tutoring provider. This study contributes to existing literature by presenting a conceptual model illustrating the interplay of these proximal factors, which can be further empirically tested.

Multimodal neuroimaging insights into the neurobiology of healthy aging across the lifespan.

The purpose of this study was to advance our understanding of the neurobiology of healthy aging, which is crucial for improving quality of life and preventing age-related diseases. Despite its importance, a comprehensive investigation of this process has yet to be fully characterized. We used a hybrid PET/MRI scanner to assess neurophysiological parameters in 80 healthy individuals aged 20-78. Cerebral amyloid-beta (Aβ) deposition and glucose metabolism were assessed using PET scans, while participants underwent simultaneous MRI scans. We found a positive correlation between Aβ-deposition and aging, and a negative correlation between glucose metabolism and aging. The insula showed the strongest negative correlation between glucose metabolism and age (Spearman's r = -0.683, 95% CI [-0.79, -0.54], p < 0.0001), while the posterior cingulate cortex had the strongest positive correlation between Aβ-deposition and age (Spearman's r = 0.479, 95% CI [0.28, 0.64], p < 0.0001). These results suggest a spatially dependent link between Aβ-deposition and metabolism in healthy older adults, indicating a compensatory mechanism in early Alzheimer's. Additionally, Aβ-deposition was linked to changes in interregional neural communication. Our study confirms previous findings on aging and offers new insights, particularly on the role of Aβ-deposition in healthy aging. We observed a linear increase in Aβ-deposition, alongside decreases in white matter integrity, cerebral blood flow, and glucose metabolism. Additionally, we identified a complex regional relationship between Aβ-deposition, glucose metabolism, and neural communication, possibly reflecting compensatory mechanisms.

Spatially resolved protein profiling in pancreatic adenosquamous carcinoma.

760 Background: Pancreatic adenosquamous carcinoma (PASC) is a rare histopathological type of pancreatic cancer that is more aggressive than pancreatic ductal adenocarcinoma (PDAC). Although PASC has a unique tumor biology and poorer prognosis, there are no guidelines for differentially treating PASC patients, and its rarity makes it significantly understudied. We used Nanostring GeoMX digital spatial profiling (DSP) to provide a targeted proteomic characterization of key tumor-promoting proteins in PASC and PDAC. Methods: FFPE tissue from PASC (n=10 primary, n= 4 met) and PDAC (n=21 primary, n=5 met) cases were analyzed using the DSP platform. Sections were stained with an 82-protein cocktail of antibodies conjugated to UV-photocleavable DNA barcodes. A pan-cytokeratin morphology marker was used to select tumor regions of interest (ROI) and inferred surrounding stromal (i.e., pan-CK negative) ROIs. UV excitation of the defined ROIs was used to release the DNA barcodes and were quantified on the NanoString nCounter system. For PASC, squamous enriched ROI were inferred from corresponding p40 IHC. Corresponding clinical and mutational status for all cases were abstracted from medical records. Results: TP53 (PDAC, 80%; PASC, 83%) and KRAS (PDAC, 76%; PASC, 100%) were the most prevalent mutations . In comparing the tumor ROIs of PASC and PDAC (all cases), DSP-assessed global expression and activation of EGFR-MAPK signaling is significantly increased in PASC, whereas PI3K-AKT signaling is significantly decreased. Compared to PDAC, EGFR expression and phosphorylation (p-EGFR), as well as p-MEK1, are significantly increased in PASC. PASC showed significantly lower levels of PLCG1 and INPP4B, while the majority of other AKT signaling effectors were unchanged. For DNA damage response signaling, PASC showed significantly higher levels of p-ATM, p-CHK2, and p21, but not p-ATR. Likewise, expression of oncoproteins c-MYC and BCL6 were significantly increased in PASC (vs. PDAC). Conclusions: Given that the normal pancreas lacks squamous cells, their histological presence is a uniquely aberrant feature that can be used to guide deep spatially-resolved interrogation of complex cellular and molecular programs. Our preliminary findings show that regions of squamous cell differentiation within PASC have intrinsically higher levels of active EGFR signaling. With emerging RAS-targeted agents poised to alter the treatment landscape, high EGFR signaling in PASC suggest a possible compensatory resistance mechanism that may require additional targeting. Likewise, reliance on ATM signaling highlights this as preferential target for DDR-directed therapies. Building on these results with additional multiomic assays will inform strategies for improving the management of patients with PASC.

Functional MRI and cognition in multiple sclerosis-Where are we now?

Multiple sclerosis-related cognitive impairment (MSrCI) affects most patients with multiple sclerosis (MS), significantly contributing to disability and socioeconomic challenges. MSrCI manifests across all disease stages, mainly impacting working memory, information processing, and attention. To date, the underlying mechanisms of MSrCI remain unclear, with its pathogenesis considered multifactorial. While conventional MRI findings correlate with MSrCI, there is no consensus on reliable imaging metrics to detect or diagnose cognitive impairment (CI). Functional MRI (fMRI) has provided unique insights into the brain's neuroplasticity mechanisms, revealing evidence of compensatory mechanisms in response to tissue damage, both beneficial and maladaptive. This review summarizes the current literature on the application of resting-state fMRI (rs-fMRI) and task-based fMRI (tb-fMRI) in understanding neuroplasticity and its relationship with cognitive changes in people with MS (pwMS). Searches of databases, including PubMed/Medline, Embase, Scopus, and the Web of Science, were conducted for the most recent fMRI cognitive studies in pwMS. Key findings ifrom rs-fMRI studies reveal disruptions in brain connectivity and hub integration, leading to CI due to decreased network efficiency. tb-fMRI studies highlight abnormal brain activation patterns in pwMS, with evidence of increased fMRI activity in earlier disease stages as a beneficial compensatory response, followed by reduced activation correlating with increased lesion burden and cognitive decline as the disease progresses. This suggests a gradual exhaustion of compensatory mechanisms over time. These findings support fMRI not only as a diagnostic tool for MSrCI but also as a potential imaging biomarker to improve our understanding of disease progression.

Specific sets of geranylgeranyl diphosphate synthases and phytoene synthases control the production of carotenoids and ABA in different tomato tissues.

Plant carotenoids are plastid-synthesized isoprenoids with roles as photoprotectants, pigments, and precursors of bioactive molecules such as the hormone abscisic acid (ABA). The first step of the carotenoid biosynthesis pathway is the production of phytoene from geranylgeranyl diphosphate (GGPP), catalyzed by phytoene synthase (PSY). GGPP produced by plastidial GGPP synthases (GGPPS) is channeled to the carotenoid pathway by direct interaction of GGPPS and PSY enzymes. Three plastid-localized GGPPS isoforms (referred to as SlG1-3) and three PSY enzymes (PSY1-3) are present in tomato (Solanum lycopersicum). Our previous work showed that SlG1 and PSY3 function together in the roots, whereas the rest of the isoforms are required in aerial tissues. Here we generated and analyzed combinations of double mutants lacking PSY1 or PSY2 and SlG2 or SlG3 to investigate the contribution of specific GGPPS and PSY pairs to the production of carotenoids and ABA in different tissues of the tomato plant. Despite that the loss of individual enzymes was found to trigger compensatory mechanisms that complicate interpretation of the results, the results confirm a major role for SlG3 in providing GGPP to PSY2 for housekeeping carotenoid biosynthesis in leaves, whereas SlG2 and PSY1 become most relevant when a more active production is required in flowers and breaker fruits, i.e., at the onset of ripening. We could also confirm that ABA production in the fruit pericarp is more dependent on PSY1 activity than on total carotenoid levels and that fruit size correlates with ABA levels accumulated in ripe rather than breaker fruits.

Gestational exposure to PM2.5, NO2, and sex steroid hormones: Identifying critical windows of exposure in the Rochester UPSIDE Cohort.

Sex steroid hormones are critical for maintaining pregnancy and optimal fetal development. Air pollutants are potential endocrine disruptors that may disturb sex steroidogenesis during pregnancy, potentially leading to adverse health outcomes. In the Environmental influences on Child Health Outcomes Understanding Pregnancy Signals and Infant Development pregnancy cohort (Rochester, NY), sex steroid concentrations were collected at study visits in early-, mid-, and late-pregnancy in 299 participants. Since these visits varied by the gestational age at blood draw, values were imputed at 14, 22, and 30 weeks gestation. Daily NO2 and PM2.5 concentrations were estimated using random forest models, with daily concentrations from each 1-km2 grid containing the subject's residence. Associations between gestational week mean NO2 and PM2.5 concentrations and sex steroid concentrations were examined utilizing distributed lag nonlinear models. Each interquartile range (IQR = 9 ppb) increase in NO2 during weeks 0-5 was associated with higher early-pregnancy total testosterone levels (cumulative β = 0.45 ln[ng/dl]; 95% CI = 0.07, 0.83), while each IQR increase in NO2 during weeks 12-14 was associated with lower early-pregnancy total testosterone levels (cumulative β = -0.27 ln[ng/dl]; 95% CI = -0.53, -0.01). Similar NO2 increases during gestational weeks 0-14 were associated with higher late-pregnancy estradiol concentrations (cumulative β = 0.29 ln[pg/ml]; 95% CI = 0.10, 0.49), while each IQR increase in NO2 concentrations during gestational weeks 22-30 was associated with lower late-pregnancy estradiol concentrations (cumulative β = -0.18 ln[pg/ml]; 95% CI = -0.34, -0.02). No associations with PM2.5 were observed, except for an IQR increase in PM2.5 concentrations (IQR = 4 µg/m3) during gestational weeks 5-11 which was associated with lower late-pregnancy estriol levels (cumulative β = -0.16 ln[ng/ml]; 95% CI = -0.31, -0.00). Residential NO2 exposure was associated with altered sex steroid hormone concentrations during pregnancy with some indication of potential compensatory mechanisms.

Cortisol and ACTH response to Dex/CRH Testing and 24-Hour Urine Free Cortisol Levels in Women with and without Premenstrual Dysphoric Disorder

HPA axis dysregulations are consistently reported in depression and other mood disorders, whereas previous studies examining HPA axis function in women with premenstrual dysphoric disorder (PMDD) have yielded inconsistent findings. In this study, we characterized the HPA axis in women with PMDD using the combined dexamethasone suppression and CRH stimulation (Dex/CRH) test and 24-hour urine free cortisol (UFC). A total of 26 women with prospectively confirmed PMDD and 25 asymptomatic controls (ACs) underwent Dex/CRH and UFC testing during both the mid-follicular and luteal phases of the menstrual cycle (MC). Primary outcomes were serial plasma cortisol and ACTH levels, their area-under-the-curve (AUC), and 24-hour UFC levels. Serial cortisol and ACTH levels were compared using a mixed model, while UFC levels and AUC of cortisol and ACTH were compared using Wilcoxon Signed Rank test. There were no significant diagnostic or menstrual cycle phase effects on plasma cortisol or ACTH levels (from time 0 to +75minutes), nor on the AUCs of plasma cortisol or ACTH (p > 0.05 for all comparisons). The PMDD group had significantly reduced 24-hour UFC levels compared to the AC group during both follicular and luteal phases (p=0.0004 and p=0.0007, respectively). Our study suggests that the pathophysiology of PMDD is distinct from that of major depression and is associated with neither exaggerated nor enhanced HPA axis activity or reactivity. Instead, we observed reduced overall HPA axis activity, which could reflect compensatory mechanisms downregulating HPA axis activity in response to chronic stress.

Robust economic scheduling model for virtual power plant considering electrolysis of molten carbonate and dynamic compensation mechanism

Robust economic scheduling model for virtual power plant considering electrolysis of molten carbonate and dynamic compensation mechanism

Beating the odds: Rare prolonged survival of truncus arteriosus: A case report with literature review.

Truncus arteriosus is a cyanotic congenital heart disease in which the great vessels of the heart fail to separate in utero. Consequently, a single truncal vessel arises from the heart to supply the systemic, coronary, and pulmonary circulations. This lesion causes the total mixing of oxygenated and deoxygenated blood, with an early onset of pulmonary vascular disease. Patients rarely survive beyond the first year of life. This case report highlights a rare survival without intervention up to the ninth year of life. We present the case of a 9-year-old male child with a history of dark discoloration of the lips and digits, easy fatigability, and fast breathing since birth. The patient is currently small for his age, with a bulging anterior chest wall, displaced apex beat, and cardiac murmur. Oxygen saturation was 57% in room air. A chest radiograph showed peri-hilar lymphadenopathy with prominent pulmonary trunks. Pack cell volume was 62%, and the gene expert test was negative. A diagnosis of cyanotic congenital heart disease, truncus arteriosus type III with pulmonary hypertension, was made after diagnostic evaluation with echocardiography. To manage congestive heart failure, the patient was put on diuretics, including furosemide and spironolactone. Parents could not carry out a definitive surgical repair due to financial constraints. Although the patient was able to survive the past year, the child had developed cardiomegaly, signs of pulmonary congestion, decreased oxygenation, and a compensatory increase in red blood cell volume. Truncus arteriosus is a critical congenital heart defect that has a high potential for morbidity and mortality within the first year of life. It requires immediate intervention and surgical repair in the immediate neonatal period. In rare cases, patients have been able to survive beyond the first year, especially if they also developed pulmonary stenosis. However, this patient had been a survivor for 9 years without another structural anomaly. Given the unique presentation and its rarity, further research is needed into compensatory mechanisms and possible low-cost and accessible alternatives in resource-constrained settings. It also demonstrates that pharmacologic therapy alone is insufficient to prevent mortality.

Combined loss of glyoxalase 1 and aldehyde dehydrogenase 3a1 amplifies dicarbonyl stress, impairs proteasome activity resulting in hyperglycemia and activated retinal angiogenesis.

Any energy consumption results in the generation of highly reactive dicarbonyls and the need to prevent excessive dicarbonyls accumulation through the activity of several interdependent detoxification enzymes. Glyoxalase 1 (GLO1) knockout zebrafish showed only moderately elevated methylglyoxal (MG) levels, but increased Aldehyde Dehydrogenases (ALDH) activity and increased aldh3a1 expression. Elevated levels of 4-hydroxynonenal (4-HNE) but no MG increase were observed in ALDH3A1KO. The question of whether ALDH3A1 prevents MG formation as a compensatory mechanism in the absence of GLO1 remained unclear. To investigate whether ALDH3A1 detoxifies MG as a compensatory mechanism in the absence of GLO1, the GLO1/ALDH3A1 double knockout (DKO) zebrafish was first generated. Various metabolites including advanced glycation end products (AGEs), as well as glucose metabolism and hyaloid vasculature were analyzed in GLO1KO, ALDH3A1KO and GLO1/ALDH3A1DKO zebrafish. In the absence of GLO1 and ALDH3A1, MG-H1 levels were increased. MG-H1 accumulation led to a severe deterioration of proteasome function, resulting in impaired glucose homeostasis and consequently amplified angiogenic activation of the hyaloid and retinal vasculature. Rescue of these pathological processes could be observed by using L-carnosine, and proteasome activator betulinic acid. The present data, together with previous studies, suggest that ALDH3A1 and GLO1 are important detoxification enzymes that prevent the deleterious effects of MG-H1 accumulation on proteasome function, glucose homeostasis and vascular function.

The Role of Immune Cells in Moyamoya Disease

Moyamoya disease (MMD) is a rare progressive cerebrovascular disorder characterized by the stenosis or occlusion of the terminal segments of the internal carotid arteries, leading to the development of abnormal collateral vascular networks. These networks are a compensatory mechanism for reduced blood flow to the brain. Despite extensive research, the exact etiology of MMD remains unknown, although recent studies suggest that immune system dysfunction plays a critical role in its pathogenesis. In particular, the involvement of immune cells such as T cells, macrophages, and dendritic cells has been increasingly recognized. These immune cells contribute to the inflammatory process and vascular remodeling observed in MMD patients, further complicating the disease’s progression. Inflammation and immune-mediated damage to the vessel walls may accelerate the narrowing and occlusion of arteries, exacerbating ischemic events in the brain. Additionally, studies have revealed that certain genetic and environmental factors can influence immune system activation in MMD, linking these pathways to disease development. This review aims to provide a comprehensive overview of the immune mechanisms at play in MMD, focusing on how immune cells participate in vascular injury and remodeling. Understanding these immunological processes may offer new therapeutic targets to halt or reverse disease progression, potentially leading to more effective treatment strategies for MMD.

Pursuing ventricular-arterial coupling: a comparison of cardiac magnetic resonance right ventricular strain analysis and novel echo-derived indexes of right ventricular myocardial work

Abstract Introduction End-systolic to arterial elastance ratio (Ees/Ea) represents right ventricular-arterial coupling (RVAC) and is the gold standard for measuring right ventricular (RV) function However, this method is time-consuming and not always readily available. A simplified approach is using the stroke volume (SV) to end-systolic volume (ESV) ratio, which has shown prognostic relevance in pts with PH, with a cut-off value of 0.5. Cardiac magnetic resonance (CMR) measurements of volumetric data allow the assessment of this ratio. CMR strain analysis has also emerged as a technique to detect subtle changes in RV function, and, recently, right ventricular myocardial work (RVMW) assessed by transthoracic echocardiography (TTE) allows the study of RV pressure-strain loops. The association between indexes of RVMW and CMR derived parameters has not yet been extensively studied, namely in pre-capillary PH population. Objectives To evaluate the relationship between the SV/ESV ratio and CMR-derived RV strain and TTE-derived RVMW in a cohort of pts with group I and group IV PH. Methods Thirteen consecutive precapillary PH pts underwent CMR, TTE and right heart catheterization prospectively. CMR feature-tracking was used to track tissue voxel motion in short and long-axis cine images, in order to derive myocardial strain. In TTE, dedicated software for left ventricle myocardial work was used for the RV. Results 69% of pts included were women, mean age 67. The average of mean PAP was 35 mmHg (± 13.5) and PVR was 4.8 WU (± 4.9). SV/ESV ratio significantly correlated with RV ejection fraction (EF) (r = 0.888, p &amp;lt; 0.001) and circumferential peak systolic (CPS) strain (r = 0.538, p = 0.037), but not with longitudinal peak systolic (LPS) strain (p = 0.571). As for TTE-derived RVMW, SV/ESV ratio demonstrated significant correlations with RVGWI (r = 0.580, p = 0.038) and RVGCW (r = 0.654, p = 0.015) but not with RVGWW (p = 0.780) nor RVGWE (p = 0.364). Significant correlations were found between RVEF and CPS strain (r = 0.690, p = 0.009), RVEF and RVGCW (r = - 0.592, p = 0.033) and between CPS strain and RVGWI (r = 0.620, p = 0.024) and RVGCW (r = 0.718, p = 0.006). 38,5% of pts had SV/ESV ratio &amp;lt; 0.5. These pts had lower RVEF (48 ± 7.1 vs 61 ± 5.5, p = 0.004), lower CPS strain (-10.9 ± 3.0 vs -15.8 ± 2.9, p = 0.015) but higher RVGWI (828 ± 167.4 vs 526 ± 192.0, p = 0.015) and RVGCW (1061 ± 228.5 vs 698 ± 141.0, p = 0.004) compared to pts with SV/ESV &amp;gt; 0.5. LPS strain, RVGWW and RVGWE did not showed statistically differences between groups. Conclusion SV/ESV ratio correlated with both CMR-derived CPS strain and TTE-derived RVMW. Pts with a lower SV/ESV ratio had lower circumferential strain but higher work indices, suggesting potential compensatory mechanisms, where increased work may not translate to efficient pumping. Further studies with larger cohorts are warranted to validate these parameters and establish relation with outcomes. Figure 1 Figure 2

Moderate aortic stenosis and preserved ejection fraction are not benign combination

Abstract Background Degenerative aortic stenosis (AS) is the most common progressive valvular disease and it is followed by adaptive left ventricular (LV) hypertrophy. LV hypertrophy is a compensatory mechanism aimed at reducing wall stress it also alters myocardial perfusion and impairs function and is tightly associated with heart failure with perserved ejection fraction (HFpEF). The outcome in patients with AS depends on the condition of the left ventricle and the presence of symptoms as well as the degree of the stenosis. Current guidelines do not address whether aortic valve replacement should be recommended in patients with moderate aortic valve stenosis regardless of the presence of symptoms and LV dysfunction. Purpose This study aimed to evaluate the association between moderate AS, symptoms, and myocardial structure and function after adjustment for comorbidities. Methods We conducted a matched cohort analysis. 61 patients with moderate aortic stenosis (MAS), LV ejection fraction &amp;lt;50% and sinus rhytm were matched with 1 comparator by age, gender and presence of arterial hypertension, diabetes, coronary artery disease, chronic obstructive pulmonary disease and renal failure. Echocardiographic parameters and presence of any of three symptoms (dyspnoea, chest pain and syncope) were recorded at and compared between two groups. Results No significant difference was found between the two groups concerning the left ventricle (LV) and right ventricle (RV) size, LV ejection fraction RV systolic function, and, pulmonary artery pressure, although patients with MAS tend to have greater end systolic diameter (ESD) but not statistically significant (35.20±8.28mm vs 32.86±6.08; P=0.083), LV global longitudinal strain was less in the MAS patients (-14.29 ±5.37 % vs. -17.95±2.44 %; P = 0.003). The LV mass index (LVMi) was greater, (122.30±31.16g/m2 vs 103.81±27.07; P=0.001), The relative wall thickness (RWT) was greater in MAS patients but not statistically significant (0.43 ± 0.09 vs. 0.41 ± 0.07 cm; P = 0.079). Left atrial volume index (LAVi) was greater in MAS (44±15ml/m2 vs 39±15; P=0.047), E/E′ ratio was greater in MAS (14±6 vs 11±3; P&amp;lt;0.001). Symptoms occurred more frequently in patients with MAS (24.6 %; 15/61 patients) than in the control group (8.2%; 5/61 patients, P=0.013). Conclusions LVEF as a means of assessing systolic function is insufficient. Ventricular hypertrophy and dysfunction were more common in patients with MAS than in the matched control group as well as the presence of symptoms. Timing of valve intervention in patients with symptomatic moderate aortic stenosis should be optimized.

Study on the effects of land use transformation on habitat quality and its driving mechanisms: a case study of the Qin-Mang River Basin

Habitat quality (HQ) is a critical factor for regional ecosystem health and sustainable development, as well as an important basis for formulating ecological protection and land-use planning. The Qin-Mang River Basin, as an integral part of the biodiversity conservation area in the Yellow River Basin, plays a significant role in maintaining the balance and stability of the regional ecosystem. This study is based on land use/land cover changes (LUCC) data from 1992, 2002, 2012, and 2022. It employs a land use transfer matrix to analyze the dynamic trends and patterns of LUCC. HQ changes are evaluated using the InVEST model, and the GeoDetector model is used to identify the key driving factors and their interactions. Additionally, spatial autocorrelation analysis is applied to explore the spatial clustering characteristics of HQ. The results indicate that between 1992 and 2022, the cumulative area of land transfer in the study area exceeded 600 km2, primarily characterized by the conversion of cultivated land to built-up areas. The HQ index decreased from 0.3409 in 1992 to 0.2896 in 2022, with a significant increase in spatial heterogeneity. Altitude, vegetation coverage, temperature, precipitation, and slope are the main driving factors influencing HQ, with natural factors dominating, but human activities gradually playing an increasingly significant role. Furthermore, HQ exhibits significant spatial clustering characteristics, with hotspot and coldspot areas providing scientific evidence for ecological protection and restoration measures. To improve HQ, it is recommended to strictly enforce ecological protection red lines, control the expansion of built-up areas, improve ecological compensation mechanisms, and promote ecological restoration measures such as returning farmland to forest and grassland.

Thyroid Endocrine Disrupting Potential of Fluoxetine in Zebrafish Larvae.

Fluoxetine (FLX), a typical selective serotonin reuptake inhibitors, has been frequently detected in aquatic environment and wild fish. However, little is known about its effect on thyroid endocrine system. In the present study, zebrafish (Danio rerio) embryos were exposed to 1, 3, 10, and 30 μg/L of FLX for 6 days. Chemical analysis demonstrated that FLX and its metabolic product (nonfluoxetine, NFLX) were accumulated in zebrafish larvae. The exposure resulted in decreased thyroid hormones (THs) levels, indicating thyroid endocrine disruption. Moreover, thyroid-stimulating hormone (TSH) content was significantly inhibited in a concentration-dependent manner after exposure to FLX. Gene transcription in the hypothalamic-pituitary-thyroid (HPT) axis was further examined, and the results showed that the genes encoding corticotrophin-releasing hormone (crh) and thyrotropin-releasing hormone (trh) were significantly up-regulated as a compensatory mechanism for the decreased TH contents accompanied with decreased tshβ mRNA expression. In addition, genes involved in thyroid hormone synthesis (sodium/iodide symporter, nis, thyroglobulin, tg) and transport (transthyretin, ttr) were down-regulated after exposure to FLX in a concentration-dependent manner. The increased gene transcription of deiodinases (dio2) and uridinediphosphate-glucuronosyltransferase (ugt1ab) might be responsible for the decrease of TH contents. In addition, a significant inhibition in thyroid hormone receptors (trα and trβ) gene expression was observed upon treatment with FLX. All these results demonstrated that FLX could alter THs and TSH content as well as gene transcription in the HPT axis, exerting an endocrine disruption of the thyroid system in zebrafish larvae.

Generation of IgM+ B cell-deficient Atlantic salmon (Salmo salar) by CRISPR/Cas9-mediated IgM knockout

Infectious diseases pose significant challenges to Norwegian Atlantic salmon aquaculture. Vaccines are critical for disease prevention; however, a deeper understanding of the immune system is essential to improve vaccine efficacy. Immunoglobulin M (IgM) is the main antibody involved in the systemic immune response of teleosts, including Atlantic salmon. In this study, we used CRISPR/Cas9 technology to knock out the two IgM genes in Atlantic salmon. High-throughput sequencing revealed an average mutagenesis efficiency of 97% across both loci, with a predominance of frameshift mutations (78%). Gene expression analyses demonstrated significantly reduced membrane-bound IgM mRNA levels in head kidney and spleen tissues. Flow cytometry revealed a 78% reduction in IgM+ B cells in peripheral blood, and Western blot analyses showed decreased IgM protein levels in serum. Notably, an upregulation of IgT mRNA was observed, suggesting a potential compensatory mechanism. This work presents the first application of CRISPR/Cas9 to disrupt an immune-related gene in the F0 generation of Atlantic salmon, and lays the foundation for generating a model completely lacking IgM+ B cells which can be used to study the role of B cells and antibodies. This study has implications for advancing immune research in teleosts and for developing strategies to improve salmon health and welfare in aquaculture.

Browning events in Arctic ecosystems: Diverse causes with common consequences

Arctic ecosystems are experiencing extreme climatic, biotic and physical disturbance events that can cause substantial loss of plant biomass and productivity, sometimes at scales of &gt;1000 km2. Collectively known as browning events, these are key contributors to the spatial and temporal complexity of Arctic greening and vegetation dynamics. If we are to properly understand the future of Arctic terrestrial ecosystems, their productivity, and their feedbacks to climate, understanding browning events is essential. Here we bring together understanding of browning events in Arctic ecosystems to compare their impacts and rates of recovery, and likely future changes in frequency and distribution. We also seek commonalities in impacts across these contrasting event types. We find that while browning events can cause high levels of plant damage (up to 100% mortality), ecosystems have substantial capacity for recovery, with biomass largely re-established within five years for many events. We also find that despite the substantial loss of leaf area of dominant species, compensatory mechanisms such as increased productivity of undamaged subordinate species lessen the impacts on carbon sequestration. These commonalities hold true for most climatic and biotic events, but less so for physical events such as fire and abrupt permafrost thaw, due to the greater removal of vegetation. Counterintuitively, some events also provide conditions for greater productivity (greening) in the longer-term, particularly where the disturbance exposes ground for plant colonisation. Finally, we find that projected changes in the causes of browning events currently suggest many types of events will become more frequent, with events of tundra fire and abrupt permafrost thaw expected to be the greatest contributors to future browning due to their severe impacts and occurrence in many Arctic regions. Overall, browning events will have increasingly important consequences for ecosystem structure and function, and for feedback to climate.

The Enhancement of the Horizontal Ecological Protection Compensation Mechanism in the Yu-Lu Section of the Yellow River Basin

Horizontal ecological compensation represents a significant institutional innovation aimed at advancing ecological civilization and serves as a key functional strategy within China’s current management framework. This paper employs the horizontal ecological protection compensation agreement of the Yu-Lu section of the Yellow River Basin as a case study. Using a game theory model and theoretical analysis, the paper explores the underlying connotations, theoretical foundations, and legal characteristics of the basin’s horizontal ecological protection compensation mechanism. This analysis reveals several challenges within the existing horizontal ecological protection compensation system in the Yellow River Basin, including the predominance of a single compensation entity, unclear compensation standards, a compensation model limited to monetary transfers, and the absence of an effective dispute resolution mechanism. This paper further examines potential improvements to the horizontal ecological protection compensation framework in the Yellow River Basin from a legal system perspective, with the aim of addressing these practical challenges and fostering the region’s ecological, environmental, and economic development.

New physiological insights using multi-TE ASL MRI measuring blood-brain barrier water exchange after caffeine intake.

Caffeine, a known neurostimulant and adenosine antagonist, affects brain physiology by decreasing cerebral blood flow. It interacts with adenosine receptors to induce vasoconstriction, potentially disrupting brain homeostasis. However, the impact of caffeine on blood-brain barrier (BBB) permeability to water remains underexplored. This study investigated the water exchange via the BBB in a perturbed physiological condition caused by caffeine ingestion, using the multiple echo time (multi-TE) arterial spin labeling (ASL) technique. Ten healthy, regular coffee drinkers (age = 31 ± 9years, 3 females) were scanned to acquire five measurements before and six measurements after caffeine ingestion. Data were analyzed with a multi-TE two-compartment model to estimate exchange time (Tex), serving as a proxy for BBB permeability to water. Additionally, cerebral blood flow (CBF), arterial transit time (ATT), and intravoxel transit time (ITT) were investigated. Following caffeine intake, mean gray matter CBF showed a significant time-dependent decrease (P < 0.01). In contrast, Tex, ATT, and ITT did not exhibit significant time-dependent change. However, a non-significant decreasing trend was observed for Tex and ITT, respectively, while ATT showed an increasing trend over time. The observed decreasing trend in Tex after caffeine ingestion suggests a potential increase in water flux across the BBB, which may represent a compensatory mechanism to maintain brain homeostasis in response to the caffeine-induced reduction in CBF. Further studies with larger sample sizes are needed to validate and expand upon these findings.

Compensatory mechanisms underlying arginine vasopressin regulation in transient polyuria during pregnancy.

Transient polyuria during pregnancy is reportedly caused by increased arginine vasopressin (AVP) degradation due to vasopressinase produced by the placenta. The mechanism underlying transient polyuria during pregnancy has not been established. In this study we measured urine volume, urine osmolality, and AVP transcriptional activity during pregnancy in wild-type and familial neurohypophysial diabetes insipidus (FNDI) mice. The FNDI mice were used as a partial AVP deficiency model. Vasopressinase was shown to be present in the placentas of pregnant mice. The Avp hnRNA level in the supraoptic nucleus, which is indicative of AVP transcriptional activity, was upregulated in wild-type and FNDI mice during late pregnancy. FNDI mice, but not wild-type mice, had a significant increase in urine volume and a decrease in urine osmolality during pregnancy. These data suggest that an increase in urine volume during pregnancy only occurs when the compensatory increase in AVP release is insufficient to counteract degradation by vasopressinase.